Aural cholesteatoma will be studied with animal models and human tissue. Skin and inflammatory granulomas will be applied to the guinea pig middle ear and the skull surface replicating conditions found in middle ear cholesteatoma to produce bone resorbing, progressively growing cysts. The animal models and human tissues will be used for morphologic and immunocytochemical studies on the light and ultrastructural level to determine the precise localization and quantitation of a specific collagenolytic enzyme. The role of inflammatory connective tissue and its interaction with migrating epithelium in collagen degradation and decalcification will be studied biochemically using inflammatory induced granulomas with and without epithelium. Collagenase from experimental granulomas will be isolated, characterized and compared to enzymes from wounds and normal skin by radioimmunoassay. Collagenase control will be studied through isolation and activation of proenzymes and enzyme inhibitors. These same tissues will be assayed concomitantly for decalcification factors. The animal bone resorbing model will be used to assess the role of skin, collagenase and decalcification factors in adjacent tissue induced bone resorption by introducing various inhibitors in vivo.